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Biomedical subjects

B Li

Publications and source records attributed to B Li.

At least 37 records · Page 2Linked to original sources
PubMed2006

A mutated human tumor necrosis factor-alpha improves the therapeutic index in vitro and in vivo.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that has cytotoxic, cytostatic and immunomodulatory effects on malignant tumors. However, clinical trials have revealed high systemic toxicity and this has hampered its utilization as an anti-cancer agent. In this study, a human TNF-alpha mutant was created and tested for its anti-tumor effects. METHODS: The TNF mutant (recombinant mutated human TNF; rmhTNF) was prepared by protein engineering in which amino acids Pro, Ser and Asp at positions 8, 9 and 10 of TNF-alpha were substituted by Arg, Lys and Arg, and C terminal Leu157 was substituted by Phe, along with deletion of the first seven N-terminal amino acids. Prokaryotic expression recombinant vector pBV-mhTNF containing the PLPR promotor was constructed and transformed into E. coli DH5alpha. The rmhTNF was expressed in a partially soluble form in DH5alpha, purified from the supernatant of cell lysate by ammonia sulfate precipitation and two sequential chromatographic steps. RESULTS: The purified rmhTNF was >95% pure by SDS-PAGE stained with silver and high-pressure size exclusion chromatography (SEC-HPLC). Its yield was about 1.22 mg/g wet cell paste. The mutant rmhTNF exhibited an approximately 50-fold increase in cytotoxicity relative to the wild-type rhTNF on the mouse fibroblast cell line L929 in a standard cytotoxicity test, and at least and at least 50 times higher LD50 as wild type rhTNF in mice. In vivo biological activity studies carried out on tumor cell transplanted mice and nude mice also showed a more effective cytotoxicity of rmhTNF than rhTNF. DISCUSSION: These results suggest that rmhTNF has potential for developing an effective anti-tumor reagent for some tumors.

Animals↗
PubMed2006

Cloning and characterization of a putative inhibitor of melanization from Anopheles gambiae.

Phenoloxidases, including tyrosinases and laccases, are enzymes involved in the synthesis of melanin, a process that can be elicited during insect immune responses, cuticle maturation, wound healing and egg chorion development. We cloned a putative inhibitor of melanization (POI) from Anopheles gambiae on the basis of homology with a functionally characterized peptide from Musca domestica (Daquinag et al., Proc Natl Acad Sci USA 1995; 92: 2964-2968). The 335 amino acid protein predicted from the A. gambiae cDNA consists of five tandemly arranged inhibitor motifs. The A. gambiae POI gene was expressed in all mosquito stages from egg to adult. POI transcript levels were high in the fat body and were measurable but comparatively reduced in the midgut. The POI transcript level increased after wounding or Sephadex bead injection. Gene knockdown did not result in faster or more extensive bead melanization but did result in more extensive melanization of wound sites following a thoracic bead injection.

Amino Acid Sequence↗
PubMed2005

Toxicity identification evaluation of five metals performed with two organisms (Daphnia magna and Lactuca sativa).

When trying to identify the main toxicants in effluents, natural waters, sediments, soil leachates, and leachates from products, the Toxicity Identification Evaluation (TIE) procedure has proven useful. To enhance the use of this procedure for soil, sewage, and sediment samples, we wanted to evaluate this TIE procedure, regarding metal toxicity, for the 96-h root elongation test performed with Lactuca sativa (lettuce) seeds. We also wanted to evaluate the effect of TIE treatment on the toxicity of Mn and Fe to Daphnia magna. Bioassays were performed with Daphnia magna (48-h immobility) and lettuce seeds (96-h root elongation) to determine the effect concentrations for both organisms of Ag, Cu, Fe, Mn, and Zn. The TIE was then performed at the determined Daphnia 48-h EC(84) and Lactuca 96-h EC(50) for each metal. Our results showed that the order of the metal toxicity was Ag>Cu>Zn>Fe>Mn, for Daphnia and Ag = Zn = Fe = Cu > Mn for lettuce seeds. We also found that toxicity of the metals for Daphnia magna was reduced according to the prevailing knowledge regarding Cu, Zn, and Ag. However, the toxicity of Ag and Cu for Daphnia was also reduced by filtration through a C18 resin. Toxicity of Mn and Fe was reduced by filtration through a CM resin and increase of pH. For lettuce seeds, toxicity of the metals was reduced by the same treatments as for Daphnia magna with the exception of EDTA addition, which did not affect Cu toxicity to lettuce seeds. No effects were found for filtration through a C18 resin. We suggest that the TIE procedure using lettuce seeds can be used in toxicity identification of metals. However, the effects of pH manipulations were often stronger with lettuce and should be interpreted with care.

Animals↗
PubMed2005

Positive assortative mating with family size as a function of predicted parental breeding values.

While other investigations have described benefits of positive assortative mating (PAM) for forest tree breeding, the allocation of resources among mates in these studies was either equal or varied, using schemes corresponding only to parental rank (i.e., more resources invested in higher-ranking parents). In this simulation study, family sizes were proportional to predicted midparent BLUP values. The distribution of midparent BLUP values was standardized by a constant, which was varied to study the range of distributions of family size. Redistributing progenies from lower- to higher-ranking families to a point where an equal number of progenies were still selected out of each family to the next generation caused minimal change in group coancestry and inbreeding in the breeding population (BP), while the additive genetic response and variance in the BP were both greatly enhanced. This generated additional genetic gains for forest plantations by selecting more superior genotypes from the BP (compared to PAM with equal family sizes) for production of improved regeneration materials. These conclusions were verified for a range of heritability under a polygenic model and under a mixed-inheritance model with a QTL contributing to the trait variation.

Analysis of Variance↗
PubMed2005

Further evidence for an HLA-related recessive mutation in nasopharyngeal carcinoma among the Chinese.

We typed 247 cases of nasopharyngeal carcinoma (NPC), a disease predominantly of the southern Chinese, and 274 controls from the Chao Shan region of China's Guangdong province for HLA A and B. Besides confirming the established associations with A2, A33, B46 and B58 (positive associations) and A11 (negative association), the results demonstrated a number of rarer alleles with strong negative association with NPC. Our data, combined with those from the previous studies in Southern Chinese, displayed the protective effects for A31 (odds ratio (OR)=0.0; 95% confidence interval (CI)=0-0.11), B13 (OR=0.50; 95% CI=0.35-0.69), B27 (OR=0.49; 95% CI=0.25-0.92), B39 (OR=0.18; 95% CI=0.06-0.48) and B55 (OR=0.32; 95% CI=0.14-0.68), the ORs comparing individuals with or without each allele. Other ethnic groups do not display such large HLA-associated variation in NPC risk. We show that a linked NPC gene with dominant mode of action could not generate such large protective effects. The results provide strong supporting evidence for the existence of a southern Chinese specific, recessive NPC gene closely linked to the HLA region as a major determinant of the Chinese risk for the disease.

China↗
PubMed2005

An investigation of valence shell orbital momentum profiles of difluoromethane by binary (e,2e) spectroscopy.

The electron binding energy spectra and momentum profiles of the valence orbitals of difluoromethane, also known as HFC32 (HFC-hydrofluorocarbon) (CH(2)F(2)), have been studied by using a high resolution (e,2e) electron momentum spectrometer, at an impact energy of 1200 eV plus the binding energy, and by using symmetric noncoplanar kinematics. The experimental momentum profiles of the outer valence orbitals and 4a(1) inner valence orbital are compared with the theoretical momentum distributions calculated using Hartree-Fock and density functional theory (DFT) methods with various basis sets. In general, the shapes of the experimental momentum distributions are well described by both the Hartree-Fock and DFT calculations when large and diffuse basis sets are used. However, the result also shows that it is hard to choose the different calculations for some orbitals, including the methods and the size of the basis sets employed. The pole strength of the ionization peak from the 4a(1) inner valence orbital is estimated.

Journal Article↗
PubMed2005

Orthotopic liver transplantation for incurable alveolar echinococcosis: report of five cases from west China.

Alveolar echinococcosis of the liver, caused by the larval stage of Echinococcus multilocularis, has the characteristics of a slow-growing liver cancer. The aim of the present work was to report a series of patients who received orthotopic liver transplantation (OLT) for life-threatening disease. Our article summarizes the medical history, diagnosis, treatment, and prognosis of five patients who received OLT between 2001 and 2002. Most patients had a long history of symptomatic disease (iterative cholangitis, obstructive jaundice) and repeated abdominal surgery. One patient died during the hospitalization mostly related to bacterial infection and multiple organ failure. Another accidental death happened 3 months later from heart failure. Three patients are alive in good condition verifying that OLT is a feasible option for these end-stage cases. In general, combination therapy-chemotherapy, interventional therapy, radical surgery or/and OLT at an early stage-is proposed in advanced cases of which OLT has clearly played a vital role. Despite major technical difficulties, OLT for incurable disease is feasible. Specific management is needed to improve the results: earlier decision for OLT in symptomatic disease, routine pre- and post-transplant therapy, reduced immunosuppression, and regular follow-up.

Adolescent↗
PubMed2005

Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy.

An antisense strategy by targeting both bcr3/abl2 and VEGF was designed to suppress the growth of Philadephia1 leukemia cells in vitro and in vivo in mice. In vitro, although bcr3/abl2 or VEGF antisense oligodeoxyribonucleotides (AS-ODNs) alone was able to inhibit the proliferation of K562 cells, the combination of bcr3/abl2 and VEGF AS-ODNs produced an additive inhibitory effect on the growth of K562 cells and significantly enhanced the sensibility of K562 cells to apoptosis-inducing stimuli including STI571. In vivo, the nude mice xenografted with K562 cells received intratumoral injections of bcr3/abl2 and VEGF AS-ODNs showed a significant reduction in leukemia tumor size and microvessel density and an increase of apoptosis in the tumors when compared to the mice that received an individual agent. These results demonstrate that targeting both bcr3/abl2 and VEGF can result in an additive tumor-suppressive action and may represent an excellent strategy to augment the efficacy of chemotherapy in CML.

Animals↗
PubMed2005

beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese.

The aim of this study was to investigate the association between polymorphisms in the beta(2)-adrenergic receptor gene (ADRB2) (-47C/T, Arg16/Gly, Gln27/Glu) and stage-2 hypertension in northern Han Chinese. We recruited 503 individuals with stage-2 hypertension and 504 age-, gender-, and area-matched controls from the International Collaborative Study of Cardiovascular Disease in Asia. Genotyping was performed using PCR-RFLP. Logistic regression analyses revealed that carriers of the Gly16 allele had a significantly higher odds ratio (OR) for hypertension, while carriers of the Glu27 allele had a significantly lower OR. In multivariate linear regression analyses, the Arg16/Gly and Gln27/Glu genotypes were significantly associated with systolic blood pressure level (p = 0.004 and p < 0.001, respectively). In haplotype analyses, we found the frequency of haplotypes composed of the Gly16 and Gln27 alleles was significantly higher, whereas the frequency of haplotypes composed of the Arg16 and Glu27 alleles was significantly lower, in hypertensives compared to their controls (both p = 0.001). These results indicate that the Gly16 and Gln27 alleles of the ADRB2 gene confer an increased risk for stage-2 hypertension in this northern Han Chinese population.

Adult↗
PubMed2005

Effects of fibrates on human organic anion-transporting polypeptide 1B1-, multidrug resistance protein 2- and P-glycoprotein-mediated transport.

The effects of different fibric acid derivatives (bezafibrate, clofibrate, clofibric acid, fenofibrate, fenofibric acid and gemfibrozil) on human organic anion transporting-polypeptide 1B1 (OATP2, OATP-C, SLC21A6), multidrug resistance protein 2 (MRP2/ABCC2) and MDR1-type P-glycoprotein (P-gp/ABCB1) were examined in vitro. Cyclosporin A (a known inhibitor of OATP1B1 and P-gp), MK-571 (a known inhibitor of MRP2) and cimetidine (an organic cation) were also tested. Bezafibrate, fenofibrate, fenofibric acid and gemfibrozil showed concentration-dependent inhibition of estradiol 17-beta-D-glucuronide uptake by OATP1B1-stably transfected HEK cells, whereas clofibrate and clofibric acid did not show any significant effects up to 100 microM. Inhibition kinetics of gemfibrozil, which exhibited the most significant inhibition on OATP1B1, was shown to be competitive with a Ki = 12.5 microM. None of the fibrates showed any significant inhibition of MRP2-mediated transport, which was evaluated by measuring the uptake of ethacrynic acid glutathione into MRP2-expressing Sf9 membrane vesicles. Only fenofibrate showed moderate P-gp inhibition as assessed by measuring cellular accumulation of vinblastine in a P-gp overexpressing cell-line. Cyclosporin A significantly inhibited OATP1B1 and P-gp, whereas only moderate inhibition was observed on MRP2. The rank order of inhibitory potency of MK-571 was determined as OATP1B1 (IC50: 0.3 microM) > MRP2 (4 microM) > P-gp (25 microM). Cimetidine did not show any effects on these transporters. In conclusion, neither MRP2- nor P-gp-mediated transport is inhibited significantly by the fibrates tested. Considering the plasma protein binding and IC50 values for OATP1B1, only gemfibrozil appeared to have a potential to cause drug-drug interactions by inhibiting OATP1B1 at clinically relevant concentrations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma.

OBJECTIVES: To search for a new clinical application of melittin (Mel): treating hepatocellular carcinoma with Mel gene. METHODS: Recombinant adenoviruses carrying the Mel gene and alpha-fetoprotein (AFP) promoter (Ad-rAFP-Mel) were constructed through a bacterial homologous recombinant system. The efficiency of adenovirus-mediated gene transfer and the inhibitory effect of Ad-rAFP-Mel on the proliferation of hepatocarcinoma cells were determined by X-gal stain and MTT assay, respectively. The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-Mel and the antitumor effect of Ad-rAFP-Mel on transplanted tumor in nude mice were detected in vivo. RESULTS: The Mel mRNA was transcribed in BEL-7402 hepatocellular carcinoma cells transducted by Ad-rAFP-Mel. The efficiency of adenovirus-mediated gene transferred to BEL-7402 cells was 100% when the multiplicity of infection of Ad-rAFP-Mel was 10 in vitro, and was also high in vivo. The inhibitive rates of Ad-rAFP-Mel and Ad-rAFP for BEL7402 cells were 66.2 +/- 2.7% and 2.9 +/- 2.3% (t=30.83, P=6.6 x 10(-6)) by MTT assay. The inhibitive rates of Ad-CMV-Mel for BEL7402, SMMC7721 and L02 cells were 58.9 +/- 9.6%, 65.9 +/- 3.8% and 31.7 +/- 1.2%, respectively, and of Ad-rAFP-Mel were 66.2 +/- 2.7%, 16.1 +/- 6.6% and 7.5 +/- 3.3%, respectively (t=1.27, P=0.27; t=11.31, P=3.5 x 10(-4); and t=12.12, P=2.7 x 10(-4) versus the Ad-CMV-Mel group in the same cells). The tumorigenicity rates of hepatocarcinoma cells transfected by Ad-rAFP-Mel were decreased. A significant antineoplastic effect was detected on transplanted tumor in nude mice by intratumoral injection of Ad-rAFP-Mel. CONCLUSIONS: Ad-rAFP-Mel can inhibit specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo. This suggests that animal toxin gene can be used as an antitumor gene.

Adenoviridae↗
PubMed2005

Identification of a new HLA-A*0201-restricted CD8+ T cell epitope from hepatocellular carcinoma-associated antigen HCA587.

For the development of peptide-based cancer immunotherapies, we aimed to identify specific HLA-A*0201-restricted CTL epitopes in hepatocellular carcinoma (HCC) associated antigen HCA587, which has been identified as a member of the cancer/testis (CT) antigens highly expressed in HCC. We first combined the use of an HLA-A*0201/peptide binding algorithm and T2 binding assays with the induction of specific CD8(+) T cell lines from normal donors by in vitro priming with high-affinity peptides, then IFN-gamma release and cytotoxicity assays were employed to identify the specific HLA-A*0201 CD8(+) T cell epitope using peptide-loaded T2 cells or the HCA587 protein(+) HCC cell line HepG2. In the six candidate synthesized peptides, two peptides showed higher binding ability in T2 binding assays. No. 2 peptide, encompassing amino acid residues FLAKLNNTV (HCA587(317-325)), was able to activate a HCA587-specific CD8(+) T-cell response in human lymphocyte cultures from two normal donors and two HCC patients, and these HCA587-specific CD8(+) T cells recognized peptide-pulsed T2 cells as well as the HCA587 protein(+) HCC cell line HepG2 in IFN-gamma release and cytotoxicity assays. The results indicate that no. 2 peptide is a new HLA-A*0201-restricted CTL epitope capable of inducing HCA587-specific CTLs. Our data suggest that identification of this new HCA587/HLA-A*0201 peptide FLAKLNNTV may facilitate the design of peptide-based immunotherapies for the treatment of HCA587-bearing HCC patients.

Antigens, Neoplasm↗
PubMed2005

Upregulation of T-bet expression in peripheral blood mononuclear cells during Vogt-Koyanagi-Harada disease.

AIM: To test the hypothesis that T-bet expression is altered in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: Peripheral blood was withdrawn from 16 VKH patients before and after immunosuppressive treatment and from 16 healthy individuals. IFN-gamma, IL-2, and IL-4 in the serum and the supernatants of peripheral blood mononuclear cells (PBMC) cultured with or without phytohaemagglutinin (PHA) were measured by ELISA. T-bet mRNA and protein expression in PBMC cultured with or without PHA was detected by RT-PCR and western blot, respectively. RESULTS: The level of IFN-gamma, but not IL-2 and IL-4, was significantly higher in the supernatants of stimulated PBMC in patients than in controls. A significantly increased T-bet mRNA was found in VKH patients during an active uveitis episode, but not in quiescent patients, compared to controls. T-bet protein was detectable in VKH patients during an active uveitis episode, but not in quiescent patients nor in the healthy controls. Stimulation of PBMC with PHA resulted in a marked upregulation of T-bet mRNA and protein expression for both patients and controls with no significant difference between the two groups. CONCLUSIONS: Upregulation of T-bet may be associated with the development of a Th1 mediated immune response in VKH disease.

Adult↗
PubMed2004

Real-time observation of dendrite coarsening in Sn-13%Bi alloy by synchrotron microradiography.

An improved synchrotron microradiography technique is being used to study dendrite growth and coarsening in Sn-13%Bi alloy in real time. The morphology of growing dendrites can be well resolved with reasonable image contrast. Dendrite arm remelting, coalescence, and fragmentation have been observed in a real alloy and in real time during solidification under controlled thermal gradients and cooling rates. This research opens a different window to the study of alloy solidification and enables unambiguous understanding of solidification processes in optically opaque, metallic alloys.

Journal Article↗
PubMed2004

New regimes of stochastic wave growth.

Stochastic-growth theory (SGT) of bursty waves is generalized and it is shown that the previously separate theory of "elementary bursts" is a limiting case. New regimes of SG are found and elucidated, and results are compared with the first relevant simulations via quasilinear theory and a reduced-parameter model. Both display stochastic behavior with the expected properties--the first simulations to demonstrate SGT behavior explicitly. Reexamination of data and simulations previously analyzed using SGT or elementary burst theory also shows good agreement with the new predictions.

Journal Article↗
PubMed2004

Mild and effective N-phthaloylation of amino acids.

In the present work various free amino acids, including tryptophan and tyrosine, were effectively N-phthaloylated under reduced pressure and at lower temperature. Moreover, under these conditions, the presence of phthalic acid in phthalic anhydride did not hinder the N-phthaloylation of amino acids. This simple process is economic, environmentally friendly, and suitable for large-scale production.

Amino Acids↗
PubMed2004

Ceramide inhibits L-type calcium channel currents in GH3 cells.

In this study, we investigated the effect of ceramide on the L-type Ca2+ channel (L-channel) in GH3 cells. We found that C6-ceramide, but not C6-dihydroceramide, the inactive analogue, had an inhibitory effect on BayK 8644-stimulated GH release. Using patch clamp analysis, C6- and C2-ceramide, but not C6-dihydroceramide, were found to inhibit the L-channel current. Increasing intracellular ceramide level with sphingomyelinase also inhibited the L-channel current. The inhibitory effect of ceramide on the L-channel current was attenuated by calphostin C, a myristolated pseudosubstrate protein kinase C (PKC) inhibitor, and lavendustin A, a tyrosine kinase inhibitor. Combined treatment with lavendustin A and the myristolated PKC inhibitor blocked the effect of ceramide on the L-channel current. These results indicate that ceramide, a lipid messenger of the sphingomyelin pathway, is an important regulator of the L-channel in GH3 cells and both tyrosine kinase and PKC are involved in this effect of ceramide.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗